ASCO 2024 research highlights

Conference speaker

As well as key findings with regards to lorlatinib for lung cancer, epcoritamab in follicular lymphoma, and pembrolizumab for bowel cancer, there were other significant study results revealed at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

RP1 and RP2 for melanoma

Replimune Group presented promising clinical data from its RP1 and RP2 clinical programmes.

Data were presented showing that the combination of RP1 and nivolumab in anti-PD-1 failed melanoma provides deep and durable responses with an “on-target” safety profile with generally transient grade 1/2 adverse events, indicative of systemic immune activation.

Approximately one third of patients experienced a response, with an overall response rate (ORR) by investigator assessment of 32.7%. In the 94 patients who had primary resistance to their immediate prior anti-PD-1 therapy, the ORR was 34%.

In the 66 patients who progressed on prior anti-PD-1 combined with anti-CTLA-4 therapy, the ORR was 27.3%. All responses lasted greater than six months from enrollment, with a median duration of response exceeding 36 months.

For RP2, the data suggest that RP2, which expresses an anti-CTLA-4 antibody, dosed both alone and in combination with an anti-PD-1 agent in metastatic uveal melanoma patients, including those with both liver and extra-hepatic metastases, had a favourable safety profile and durable anti-tumour activity.

RP2 administered as monotherapy or in combination with nivolumab demonstrated an ORR of 29.4%, with a disease control rate (DCR) of 58.8%.

Tecartus for B-cell acute lymphoblastic leukaemia

Kite announced four-year overall survival (OS) data from the pivotal ZUMA-3 study evaluating the CAR T-cell therapy Tecartus (brexucabtagene autoleucel) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia (R/R B-ALL).

The findings showed a median OS of 25.6 months and a four-year OS rate of 40% in all treated patients, with a safety profile consistent with that observed in the three-year analysis.

For patients treated with the pivotal dose of brexucabtagene autoleucel in the pooled analysis Phase I and II, the median follow-up time was 53.6 months (range 44.7-82.3) with four-year minimum follow-up. Among all treated patients, the median OS was 25.6 months, and 47 months in patients with complete remission or complete remission with incomplete haematologic recovery, the primary endpoint.

Medians for OS in patients with and without prior blinatumomab were 15.9 and 60.4 months, respectively. Median OS was 36.3 months in responders who went on to subsequent allogeneic stem cell transplant and 60.4 months (23.2-NE) in those who did not.

Yescarta for central nervous system lymphoma

Kite also announced data from a pilot study in collaboration with Dana-Farber Cancer Institute, that demonstrate Yescarta (axicabtagene ciloleucel) is well-tolerated in patients living with relapsed or refractory (R/R) primary or secondary central nervous system lymphoma (PCNSL and SCNSL).

The prognosis of PCNSL has historically been poor with a five-year survival rate of only 30%. More than half of the patients experience a relapse after front-line treatment, with a median survival of approximately two months.

In this pilot study of 18 patients with CNSL, at a median follow-up of 24.2 months, no treatment-limiting toxicities and no apparent additional risk of adverse events were reported.

The objective response rate was 94.4% and the complete response rate was 66.7%. The median time to best response was three months. The median duration of response was 13.4 months and nine patients had progressed. At a median follow-up of 24 months, the median progression-free survival was 14.3 months and median overall survival was 26.4 months.

Enhertu for metastatic breast cancer

Daiichi Sankyo and AstraZeneca’s shared positive results from the DESTINY-Breast06 Phase III trial showing that Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard of care chemotherapy in patients with HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) metastatic breast cancer.

In the primary endpoint analysis of patients with HR positive, HER2 low metastatic breast cancer, Enhertu reduced the risk of disease progression or death by 38% versus chemotherapy. Median PFS was 13.2 months in the ENHERTU arm compared to 8.1 months in the chemotherapy arm as assessed by blinded independent central review (BICR).

In the key secondary endpoint analysis of PFS by BICR in the overall trial population, Enhertu achieved a similar 37% reduction in the risk of disease progression or death versus chemotherapy with a median PFS of 13.2 months in the Enhertu arm versus 8.1 months with chemotherapy.

Rybrevant for non-small cell lung cancer

Janssen-Cilag announced new data from the Phase III MARIPOSA study demonstrating the efficacy of first-line treatment with Rybrevant (amivantamab) in combination with lazertinib in patients with high-risk disease or clinical features, which occur in nearly 85% of patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.

Results from the new analysis show the amivantamab-combination consistently and significantly improved PFS compared to osimertinib in patients with NSCLC with EGFR exon 19 deletion (ex19del) or L858R mutations.

The MARIPOSA study enrolled treatment-naïve patients with EGFR-mutant (ex19del or L858R) advanced NSCLC. Overall, results showed amivantamab plus lazertinib resulted in a significant reduction in the risk of disease progression or death compared to osimertinib as previously reported.

Osemitamab for G/GEJ cancer

Transcenta announced the results from the Phase I/IIa Cohort-G data for Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment of patients with advanced G/GEJ cancer.

The study, which enrolled patients regardless of their CLDN18.2 and PD-L1 CPS expression, indicated encouraging efficacy data for the triple combination, especially in patients with high or medium (H/M) CLDN18.2 expression, regardless of their PD-L1 CPS value.

The results showed that median progression-free survival reached 12.6 months in patients with H/M CLDN18.2 expression, any PD-L1 CPS, as well as in the 80% of patients with PD-L1 CPS<5.

Using the group of patients with very low/no CLDN18.2 expression as surrogate control, the HR for the triple combination is 0.443 in favour of the H/M expressors and in these patients, the confirmed overall response rate was 68%.

Combination immunotherapy for colorectal cancer

Data were presented from a study led by UCLA Health Jonsson Comprehensive Cancer Center researchers, which found that using a combination of experimental immunotherapy drugs with chemotherapy significantly improves progression-free survival and overall survival for patients with metastatic colorectal cancer who have previously undergone standard chemotherapy treatment when compared to those who received the targeted therapy regorafenib alone.

The novel treatment combination, called EZFB, consists of etrumadenant (E), a dual A2a/A2b adenosine receptor antagonist, zimberelimab (Z), an immune checkpoint inhibitor, and a chemotherapy regimen (FB: mFOLFOX-6 ± bevacizumab),

The median PFS with the combination treatment was 6.2 months compared to 2.1 months for those in the targeted therapy only group.

The median OS with the combination treatment was 19.7 months as compared to 9.5 months for those in the targeted therapy only group.

The results of the study also showed treatment with the novel combination therapy either partially or completely shrank tumours in 17.3% of patients. For patients on regorafenib only, 2.7% had tumour shrinkage.

BOXR1030 for solid tumours

SOTIO Biotech presented a Trial-in-Progress poster on the first-in-human DUET-01 Phase I/II study evaluating the use of BOXR1030, a metabolically enhanced CAR T-cell therapy, for the treatment of patients with solid tumours.

Patient enrolment and dosing in the DUET-01 clinical trial (NCT05120271) are ongoing at three leading cancer care centres across the US, with additional sites expected to be imminently initiated in the UK.

The DUET-01 clinical trial is a first-in-human, open-label, multicentre, dose escalation study to assess and determine the recommended Phase II dose of BOXR1030 in patients with GPC3-positive advanced solid tumours.

The trial will enrol up to 98 patients with advanced, unresectable hepatocellular carcinoma, squamous cell lung cancer, myxoid/round cell liposarcoma, and Merkel cell carcinoma.

Diana Spencer, Senior Digital Content Editor, DDW

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